Table 1.

Classification of cross-linkers

Type	Examples	Mechanism of action	Advantages	Disadvantages
Physical	1. Dehydrothermal treatment (DHT)	Cross-linking by forming non-covalent bonds.	1. Safe.	1. Weak resistance to collagenase [68].
	2. Ultraviolet irradiation (UV)		2. Non-toxic to cells.	2. Excessive temperature tends to cause collagen denaturation.
			3. Gentler action than chemical cross-linking.	3. Poor crosslinking strength and durability.
			4. Inexpensive.
			5. Extended biodegradation of scaffolds.
Chemical	1. Glutaraldehyde (GA)	Binds to chemical bond during cross-linking, leaves the chemical bond after cross-linking [97].	1. Virtually non-toxic to cells.	1. Potential cytotoxicity to cells.
	2. Carbodiimide (EDC)		2. Stronger cross-linking effect.	2. Costly.
	3. Nhydroxysuccinimide (NHS)		3. Strong resistance to collagenase.	3. Require thorough washing to remove cross-linkers.
Biological	1. Genipin	Cross-linking of two amide bonds formed by nucleophilic attack of the amine with two amino groups [89].	1. Natural sources.	1. Excessive concentration can lead to a decrease in the mechanical strength of the scaffolds.
	2. Transglutaminase (TG)		2. Good biocompatibility.	2. Blue reaction after cross-linking.
	3. Plant-derived proanthocyanidins (PACs)		3. Very low cytotoxicity.